Assessment of the Independent and Synergistic Effects of Fluid Overload and Acute Kidney Injury on Outcomes of Critically Ill Children Objectives: Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients. Design: Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study. Setting: Single-center quaternary level PICU. Patients: One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days. Interventions: None. Measurements and Main Results: Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload+ patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload– patients, regardless of acute kidney injury status. Fluid overload+/acute kidney injury– patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload+/acute kidney injury+ patients compared with patients without both classifications (17.4; 95% CI, 11.0–23.7 vs 8.8; 95% CI, 7.3–10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality. Conclusions: The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Database support was provided from the Center for Clinical and Translational Science Training Grant Support (8UL1-TR000077). Dr. Gist received support for article research from the National Institutes of Health. Dr. Menon was sponsored in the Cincinnati Children’s Hospital Medical Center’s Acute Care Nephrology Fellowship through a grant from Gambro Renal Products. Dr. Basu received funding from BioPorto Diagnostics and Baxter Healthcare. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: rajit.basu@choa.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Fluid Overload in Pediatric Severe Traumatic Brain Injury Objective: Pediatric traumatic brain injury is a major public health problem in the United States. Hypertonic saline therapy is a well-established treatment in patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) who have intracranial hypertension. In children, fluid overload is associated with increased mortality, ventilator duration, and length of PICU stay, even when controlling for severity of illness. This study reports prevalence of fluid overload in pediatric patients with severe traumatic brain injury treated with 3% hypertonic saline and effect on clinical outcomes. Design: Single-center retrospective chart review. Setting: PICUs at two tertiary children’s hospitals. Patients: One hundred thirty-eight patients with traumatic brain injury with postresuscitation Glasgow Coma Scale less than or equal to 8 who received hypertonic saline from September 1, 2010, to February 28, 2016, and intracranial pressure monitoring and survived at least 24 hours from admission. Interventions: None. Measurements and Main Results: We used fluid balance percentage greater than or equal to 10% as our definition of fluid overload. Ninety-one percent of patients less than 1 year old had fluid overload on day 10 of admission compared with 47% of patients greater than 1 year. Fluid overloaded patients did not have increased mortality, acute kidney injury, PICU length of stay, or ventilator days. Hypertonic saline was not the cause of fluid overload in these patients. Conclusions: Patients with severe traumatic brain injury do have high rates of fluid overload. However, fluid overload did not contribute to mortality, longer days on the ventilator, increased risk of acute kidney injury, or increased PICU length of stay. Dr. Williamson received $1,500 in internal grant support from the Department of Anesthesiology at Emory University for an unrelated project. Dr. Paden received multiple patents (both issued and pending) and multiple grants, all of which are not related to this project. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: caseystulce@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Transcranial Doppler Ultrasound During Critical Illness in Children: Survey of Practices in Pediatric Neurocritical Care Centers Objectives: The scope of transcranial Doppler ultrasound in the practice of pediatric neurocritical care is unknown. We have surveyed pediatric neurocritical care centers on their use of transcranial Doppler and analyzed clinical management practices. Design: Electronic-mail recruitment with survey of expert centers using web-based questionnaire. Setting: Survey of 43 hospitals (31 United States, 12 international) belonging to the Pediatric Neurocritical Care Research Group. Patients: None. Interventions: None. Measurements and Main Results: A 67% (29/43) hospital-response rate. Of these centers, 27 reported using transcranial Doppler in the PICU; two hospitals opted out due to lack of transcranial Doppler availability/use. The most common diagnoses for using transcranial Doppler in clinical care were intracranial/subarachnoid hemorrhage (20 hospitals), arterial ischemic stroke (14 hospitals), and traumatic brain injury (10 hospitals). Clinical studies were carried out and interpreted by credentialed individuals in 93% (25/27) and 78% (21/27) of the centers, respectively. A written protocol for performance of transcranial Doppler in the PICU was available in 30% (8/27 hospitals); of these, two of eight hospitals routinely performed correlation studies to validate results. In 74% of the centers (20/27), transcranial Doppler results were used to guide clinical care: that is, when to obtain a neuroimaging study (18 hospitals); how to manipulate cerebral perfusion pressure with fluids/vasopressors (13 hospitals); and whether to perform a surgical intervention (six hospitals). Research studies were also commonly performed for a range of diagnoses. Conclusions: At least 27 pediatric neurocritical care centers use transcranial Doppler during clinical care. In the majority of centers, studies are performed and interpreted by credentialed personnel, and findings are used to guide clinical management. Further studies are needed to standardize these practices. The Executive Committee of the Pediatric Neurocritical Care Research Group (PNCRG) includes: the Chair (Michelle Schober, 2018-2020), a past Chair (Courtney Robertson, 2016-2018), Secretary/Treasurer (Jonathan Kurz, 2019-2021), the Chair of the Scientific Review Committee (Jose Pineda, 2018-2020) and two Councilors (senior level leaders, Mark Wainwright and Mike Bell). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Dr. Appavu’s institution received funding from American Heart Association and Moberg ICU Solutions. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kerri.larovere@childrens.harvard.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Apneic Oxygenation As a Quality Improvement Intervention in an Academic PICU Objectives: To evaluate if the use of apneic oxygenation during tracheal intubation in children is feasible and would decrease the occurrence of oxygen desaturation. Design: Prospective pre/post observational study. Setting: A large single-center noncardiac PICU in North America. Patients: All patients less than 18 years old who underwent primary tracheal intubation from August 1, 2014, to September 30, 2018. Interventions: Implementation of apneic oxygenation for all primary tracheal intubation as quality improvement. Measurements and Main Results: Total of 1,373 tracheal intubations (661 preimplementation and 712 postimplementation) took place during study period. Within 2 months, apneic oxygenation use reached to predefined adherence threshold (> 80% of primary tracheal intubations) after implementation and sustained at greater than 70% level throughout the postimplementation. Between the preimplementation and postimplementation, no significant differences were observed in patient demographics, difficult airway features, or providers. Respiratory and procedural indications were more common during preintervention. Video laryngoscopy devices were used more often during the postimplementation (pre 5% vs post 75%; p < 0.001). Moderate oxygen desaturation less than 80% were observed in fewer tracheal intubations after apneic oxygenation implementation (pre 15.4% vs post 11.8%; p = 0.049); severe oxygen desaturation less than 70% was also observed in fewer tracheal intubations after implementation (pre 10.4% vs post 7.2%; p = 0.032). Hemodynamic tracheal intubation associated events (i.e., cardiac arrests, hypotension, dysrhythmia) were unchanged (pre 3.2% vs post 2.0%; p = 0.155). Multivariable analyses showed apneic oxygenation implementation was significantly associated with a decrease in moderate desaturation less than 80% (adjusted odds ratio, 0.55; 95% CI, 0.34–0.88) and with severe desaturation less than 70% (adjusted odds ratio, 0.54; 95% CI, 0.31–0.96) while adjusting for tracheal intubation indications and device. Conclusions: Implementation of apneic oxygenation in PICU was feasible, and was associated with significant reduction in moderate and severe oxygen desaturation. Use of apneic oxygenation should be considered when intubating critically ill children. Supported, in part, by grant from the Agency for Healthcare Research and Quality (AHRQ) R03HS021583, AHRQ R18HS022464, R18HS024511 and Endowed Chair, Critical Care Medicine, The Children’s Hospital of Philadelphia. Ms. Napolitano’s, Ms. Craig’s, and Dr. Nishisaki’s institutions received funding from Agency for Healthcare Research and Quality (AHRQ) R03HS021583, AHRQ R18HS022464, and R18HS024511. Ms. Napolitano’s and Ms. Craig’s institutions received funding from Endowed Chair, Critical Care Medicine, The Children’s Hospital of Philadelphia. Ms. Napolitano and Drs. Nadkarni and Nishisaki are supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development R21 HD089151 and AHRQ R18HS024511. Ms. Napolitano disclosed off-label product use of simple nasal cannula with higher flow ranges than recommended by the manufacturer; and she disclosed that she has research relationships and consulting relationships with Draeger, Actuated Medical, Smiths Medical, Vero Biotech, Philips/Respironics, and Aerogen. Ms. Snyder disclosed that she received compensation from American Association of Critical-Care Nursing (presenting at National Training Institute in 2017) and Springer Publishing for writing a chapter on pediatric sepsis. Dr. Branca received support for article research from AHRQ R03HS021583, AHRQ R18HS022464, and R18HS024511. Dr. Nishisaki received support for article research from the AHRQ. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: napolitanon@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Parental Conflict, Regret, and Short-term Impact on Quality of Life in Tracheostomy Decision-Making Objectives: The prevalence of tracheostomy-dependence in critically ill children is increasing in the United States. We do not know the impact of this decision on parental outcomes. We aimed to determine the prevalence of decisional conflict and regret and explore the impact on quality of life among parents considering tracheostomy placement for their child. Subjects: Parents facing tracheostomy decision for their child. Design: Prospective, mixed-methods longitudinal study. Setting: PICU, cardiac ICU, and neonatal ICU of a single quaternary medical center. Interventions: None. Measurements and Main Results: Parents completed a decisional conflict survey at the time of tracheostomy decision and decisional regret and quality of life surveys at 2 weeks and 3 months after the decision regarding tracheostomy placement was made. We enrolled 39 parents, of which 25 completed surveys at all three time points. Thirty-five of 39 (89.7%) reported at least some decisional conflict, most commonly from feeling uninformed and pressured to make a decision. At 2 weeks, 13 of 25 parents (52%) reported regret, which increased to 18 of 25 participants (72%) at 3 months. Regret stemmed from feeling uninformed, ill-chosen timing of placement, and perceptions of inadequate medical care. At 2 weeks, the quality of life score was in the mid-range, 78.8 (SD 13.8) and decreased to 75.5 (SD 14.2) at 3 months. Quality of life was impacted by the overwhelming medical care and complexity of caring for a child with a tracheostomy, financial burden, and effect on parent’s psychosocial health. Conclusions: The decision to pursue tracheostomy among parents of critically ill children is fraught with conflict with worsening regret and quality of life over time. Strategies to reduce contributing factors may improve parental outcomes after this life-changing decision. This work was performed at Department of Critical Care Medicine, Children’s National Health Systems, 111 Michigan Avenue NW, Suite M4800, Washington, DC 20010. Supported, in part, by grant 1K23HD080902 from the National Institutes of Health and grant UL1TR0001876 from the National Center for Advancing Translational Sciences to the Clinical and Translational Science Institute at Children’s National Health Systems. Dr. October’s institution received funding from National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Services; she received funding from National Center for Advancing Translational Sciences, Clinical and Translational Science Institute at Children’s National Health Systems; and she received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Tessie W. October, MD, MPH, Department of Critical Care Medicine, Children’s National Health Systems, 111 Michigan Avenue NW, Suite M4800, Washington, DC 20010. E-mail: toctober@childrensnational.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Platelet Transfusion Practice and Related Outcomes in Pediatric Extracorporeal Membrane Oxygenation Objective: To describe factors associated with platelet transfusion during pediatric extracorporeal membrane oxygenation and the relationships among platelet transfusion, complications, and mortality. Design: Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014. Setting: Eight Collaborative Pediatric Critical Care Research Network–affiliated hospitals. Patients: Age less than 19 years old and treated with extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Of 511 children, 496 (97.1%) received at least one platelet transfusion during extracorporeal membrane oxygenation. Neonatal age, venoarterial extracorporeal membrane oxygenation, and various acute and chronic diagnoses were associated with increased average daily platelet transfusion volume (milliliters per kilogram body weight). On multivariable analysis, average daily platelet transfusion volume was independently associated with mortality (per 1 mL/kg; odds ratio, 1.05; CI, 1.03–1.08; p < 0.001), whereas average daily platelet count was not (per 1 × 109/L up to 115 × 109/L; odds ratio, 1.00; CI, 0.98–1.01; p = 0.49). Variables independently associated with increased daily bleeding risk included increased platelet transfusion volume on the previous extracorporeal membrane oxygenation day, a primary cardiac indication for extracorporeal membrane oxygenation, adolescent age, and an acute diagnosis of congenital cardiovascular disease. Variables independently associated with increased daily thrombotic risk included increased platelet transfusion volume on the previous extracorporeal membrane oxygenation day and venoarterial extracorporeal membrane oxygenation. Variables independently associated with decreased daily thrombotic risk included full-term neonatal age and an acute diagnosis of airway abnormality. Conclusions: Platelet transfusion was common in this multisite pediatric extracorporeal membrane oxygenation cohort. Platelet transfusion volume was associated with increased risk of mortality, bleeding, and thrombosis. Other board members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) are: Robert Berg, MD, Department of Anesthesia and Critical Care, Children’s Hospital of Philadelphia, Philadelphia, PA; Peter Mourani, MD, Department of Pediatrics, Denver Children’s Hospital, University of Colorado, Denver, CO; Anil Sapru, MD, Department of Pediatrics, UCLA Mattel Children’s Hospital, University of California, Los Angeles, CA; and Mark Hall, MD, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus OH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Supported, in part, by the following cooperative agreements from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services: U10HD050096, U10HD049981, U10HD049983, U10HD050012, U10HD063108, U10HD063106, U10HD063114, and U01HD049934. Drs. Dalton, Newth, and Carcillo’s institution received funding from the National Institute of Child Health and Human Development. Dr. Dalton disclosed off label product use of extracorporeal membrane oxygenation (ECMO), and she received funding from Innovative ECMO Concepts. Drs. Dalton, Reeder, Zuppa, Shanley, Newth, Pollack, Wessel, Carcillo, Harrison, Dean, and Meert received support for article research from the National Institutes of Health (NIH). Drs. Reeder, Zuppa, Shanley, Pollack, Wessel, Harrison, Dean, and Meert’s institution received funding from the NIH. Dr. Shanley received funding from PAS, IPRF, and Springer. Dr. Newth received funding from Philips Research North America (consulting). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kmeert@med.wayne.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure Objectives: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis. Design: Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure. Setting: Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Patients: Children with severe sepsis and indwelling arterial or central venous catheters. Interventions: Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge. Measurements and Main Results: Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06–6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72–18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35–4.08). Conclusions: These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Supported, in part, by grant R01GM108618 (to Dr. Carcillo) from the National Institutes of General Medical Sciences, by 5U01HD049934-10S1 from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services and the following cooperative agreements: U10HD049983, U10HD050096, U10HD049981, U10HD063108, U10HD63106, U10HD063114, U10HD050012, and U01HD049934. Drs. Carcillo’s, Berg’s, Wessel’s, Pollack’s, Meert’s, Hall’s, Doctor’s, Cornell’s, Harrison’s, Zuppa’s, Reeder’s, Banks’s, and Holubkov’s institutions received funding from the National Institutes of Health (NIH). Drs. Carcillo’s, Newth’s, Shanley’s, and Dean’s institutions received funding from the National Institutes of Child Health and Human Development. Drs. Carcillo, Berg, Wessel, Polack, Meert, Hall, Newth, Doctor, Shanley, Cornell, Harrison, Zuppa, Reeder, Banks, Holubkov, Notterman, and Dean received support for article research from the NIH. Dr. Carcillo’s institution also received funding from the National Institutes of General Medical Sciences. Dr. Pollack disclosed that his research is supported by philanthropy from Mallinckrodt Pharmaceuticals. Dr. Hall received funding from Bristol Myers-Squibb (for service on an advisory board) and LaJolla Pharmaceuticals (service as a consultant), both unrelated to the current submission. Dr. Newth received funding from Philips Research North America. Dr. Doctor’s institution received funding from the Department of Defense and Kalocyte. Dr. Shanley received funding from Springer publishing, International Pediatric Research Foundation, and Pediatric Academic Societies. Dr. Cornell disclosed he is co-founder of Pre-Dixon Bio. Dr. Holubkov received funding from Pfizer (Data Safety Monitoring Board [DSMB] member), Medimmune (DSMB member), Physicians Committee for Responsible Medicine (biostatistical consulting), DURECT Corporation (biostatistical consulting), Armaron Bio (DSMB past member), and St Jude Medical (DSMB past member). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: carcilloja@ccm.upmc.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Performance of an Automated Screening Algorithm for Early Detection of Pediatric Severe Sepsis Objectives: To create and evaluate a continuous automated alert system embedded in the electronic health record for the detection of severe sepsis among pediatric inpatient and emergency department patients. Design: Retrospective cohort study. The main outcome was the algorithm’s appropriate detection of severe sepsis. Episodes of severe sepsis were identified by chart review of encounters with clinical interventions consistent with sepsis treatment, use of a diagnosis code for sepsis, or deaths. The algorithm was initially tested based upon criteria of the International Pediatric Sepsis Consensus Conference; we present iterative changes which were made to increase the positive predictive value and generate an improved algorithm for clinical use. Setting: A quaternary care, freestanding children’s hospital with 404 inpatient beds, 70 ICU beds, and approximately 60,000 emergency department visits per year Patients: All patients less than 18 years presenting to the emergency department or admitted to an inpatient floor or ICU (excluding neonatal intensive care) between August 1, 2016, and December 28, 2016. Intervention: Creation of a pediatric sepsis screening algorithm. Measurements and Main Results: There were 288 (1.0%) episodes of severe sepsis among 29,010 encounters. The final version of the algorithm alerted in 9.0% (CI, 8.7–9.3%) of the encounters with sensitivity 72% (CI, 67–77%) for an episode of severe sepsis; specificity 91.8% (CI, 91.5–92.1%); positive predictive value 8.1% (CI, 7.0–9.2%); negative predictive value 99.7% (CI, 99.6–99.8%). Positive predictive value was highest in the ICUs (10.4%) and emergency department (9.6%). Conclusions: A continuous, automated electronic health record-based sepsis screening algorithm identified severe sepsis among children in the inpatient and emergency department settings and can be deployed to support early detection, although performance varied significantly by hospital location. Drs. Eisenberg and Madden contributed equally to this work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). Cerner Corporation provided project management and statistical support for this project. Dr. Christianson disclosed work for hire, and he disclosed that he was employed by Cerner Corporation, which is the developer of the Millennium electronic health record system implemented at the study site. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: matthew.eisenberg@childrens.harvard.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Developing Pediatric Critical Care in Kenya Objective: To describe efforts to improve the care of critically ill children in a tertiary care public hospital in a resource-limited setting. Design: Descriptive. Setting: Pediatric wards at the Kenyatta National Hospital in Nairobi, Kenya. Patients: Critically ill children admitted to the hospital. Interventions: A graduated approach to improving critical care capacity in a resource-limited setting. Measurements and Main Results: Pediatric mortality was tracked in the adult ICU and PICU following the engagement of a pediatric intensivist and creation of a critical care team. Mortality declined from 76.2% to 37.5% in the first 2 years of the new PICU. Conclusions: Caring for critically ill children in resource-limited setting presents many challenges. The stepwise approach described here has led to a nearly 50% reduction in mortality among critically ill children at Kenyatta National Hospital. It is a viable strategy to begin to address the disproportionate number of critically ill and injured children in resource-limited setting. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: drrash_21@yahoo.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

A Machine Learning-Based Triage Tool for Children With Acute Infection in a Low Resource Setting Objectives: To deploy machine learning tools (random forests) to develop a model that reliably predicts hospital mortality in children with acute infections residing in low- and middle-income countries, using age and other variables collected at hospital admission. Design: Post hoc analysis of a single-center, prospective, before-and-after feasibility trial. Setting: Rural district hospital in Rwanda, a low-income country in Sub-Sahara Africa. Patients: Infants and children greater than 28 days and less than 18 years of life hospitalized because of an acute infection. Interventions: None. Measurements and Main Results: Age, vital signs (heart rate, respiratory rate, and temperature) capillary refill time, altered mental state collected at hospital admission, as well as survival status at hospital discharge were extracted from the trial database. This information was collected for 1,579 adult and pediatric patients admitted to a regional referral hospital with an acute infection in rural Rwanda. Nine-hundred forty-nine children were included in this analysis. We predicted survival in study subjects using random forests, a machine learning algorithm. Five prediction models, all including age plus two to five other variables, were tested. Three distinct optimization criteria of the algorithm were then compared. The in-hospital mortality was 1.5% (n = 14). All five models could predict in-hospital mortality with an area under the receiver operating characteristic curve ranging between 0.69 and 0.8. The model including age, respiratory rate, capillary refill time, altered mental state exhibited the highest predictive value area under the receiver operating characteristic curve 0.8 (95% CI, 0.78–0.8) with the lowest possible number of variables. Conclusions: A machine learning-based algorithm could reliably predict hospital mortality in a Sub-Sahara African population of 949 children with an acute infection using easily collected information at admission which includes age, respiratory rate, capillary refill time, and altered mental state. Future studies need to evaluate and strengthen this algorithm in larger pediatric populations, both in high- and low-/middle-income countries. The views expressed in this publication are those of the author(s) and not necessarily those of African Academy of Sciences, New Partnership for Africa’s Development Agency, Wellcome Trust, or the UK government. Supported, in part, by grant from the Life Priority Fund, the Hellman Foundation, and the King Baudouin Foundation. The research project was supported by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine through the Surviving Sepsis Campaign. Dr. Kwizera disclosed that he is supported by The Developing Excellence in Leadership, Training and Science (DELTAS) Africa Initiative grant number DEL-15-011 to Training Health Researchers into Vocational Excellence in East Africa-2. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences Alliance for Accelerating Excellence in Science in Africa and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency with funding from the Wellcome Trust grant number 107742/Z/15/Z and the UK government. Dr. Patterson disclosed that the Surviving Sepsis in Resource Limited Environments project was supported by grants from the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM), with the SCCM grant supported by a donation from the Hellman Foundation. He disclosed that his son and daughter have participated in infrastructure development and education projects in Gitwe, Rwanda that were funded by the Hellman Foundation. Ms. Harmon’s institution received funding from Hellman Foundation (Judith Hellman principal) and King Baudouin Foundation through ESICM, and she received other support in the form of supplies for the clinics and hospital in the amount of $10,000 from the Becton Dickinson Corporation. Dr. Duenser received funding from Life Priority Fund, Hellman Foundation, and King Baudouin, all of which were paid to the Surviving Sepsis Campaign. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Martin W. Dünser, MD, DESA, EDIC, Department of Anesthesiology and Intensive Care Medicine, Kepler University Hospital and Johannes Kepler University Linz, Krankenhausstrasse 9, 4040 Linz, Austria. E-mail: Martin.Duenser@kepleruniklinikum.at ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies